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Thyroid [123I]MIBG uptake is proposed as a tool for differentiating between Parkinson's disease (PD) and diabetes mellitus (DM) on [123I]MIBG scintigraphies since both patient groups show decreased cardiac uptake. One study compared thyroid [123I]MIBG uptake in DM and PD patients and reported reduced [123I]MIBG uptake only in the PD group. Here, we investigated thyroid [123I]MIBG uptake in patients with PD and DM and found severely reduced thyroid [123I]MIBG uptake in DM. Larger studies are needed to substantiate whether DM patients are more or less likely to exhibit decreased thyroid MIBG uptake compared to controls and PD patients.

Creating a single complete denture against natural dentition can be challenging. To facilitate the clinical procedure and promote balanced occlusion, we developed a digital workflow of a single complete denture using a multi-functional diagnostic denture (DD). The DD was digitally designed and fabricated using a three-dimensional printing process to create a guide for tooth grinding in opposing dentition and a final impression that allows the jaw relationship and dynamic articulation to be recorded by an intraoral scanner. The definitive complete denture was combined with a milled artificial dentition and titanium-plated denture base. Within three clinical visits, this digital workflow provided better efficiency and easy implementation for a single complete denture.

Three-dimensional (3D) cell culture systems are reported to be more physiologically similar to the in vivo state than 2-dimensional (2D) models, which are extensively employed in periodontal research. Herein, we developed a 3D gingival tissue model with both epithelial and lamina propria layers using human gingival epithelial Ca9-22 cells and primary gingival fibroblasts. The epithelial layer of the developed 3D gingival tissue culture was treated with butyrate, a metabolite of oral bacteria, and the treatment induced the release of damage-associated molecular patterns, such as DNA and Sin3A associated protein 130 kDa (SAP130). Taken together, butyrate exposure to the epithelium of 3D gingival epithelial-connective tissue hybrid systems could induce epithelial cell death and the subsequent release of damage-associated molecular patterns.

The physiological processes involved in adaptation to osmotic pressure in euryhaline crustaceans are highly energy demanding, but the effects of dietary lipids (fat) on low salinity adaptations have not been well evaluated. In the present study, a total of 120 mud crabs (Scylla paramamosain, BW = 17.87 ± 1.49 g) were fed control and high-fat (HF) diets, at both medium salinity (23‰) and low salinity (4‰) for 6 wk, and each treatment had 3 replicates with each replicate containing 10 crabs. The results indicated that a HF diet significantly mitigated the reduction in survival rate, percent weight gain and feed efficiency induced by low salinity (P

BACKGROUND: In 2021, atypical seasonal respiratory syncytial virus (RSV) outbreaks were observed in several countries. However, the peak, duration, and severity of these outbreaks have not been assessed. METHODS: Data were collected from almost all facilities with pediatric wards in Saitama Prefecture, Japan. Variables included the weekly number of patients admitted with RSV infection, their age, and the number of patients who required intubation. The average weekly admission rates (number of patients admitted divided by the number of hospitals) were compared by pre-pandemic year (2018 and 2019) and 2021, using analysis of variance. RESULTS: In 2021, 1354 patients were admitted with RSV infection. The median age of the patients was < 12 months. The admission rate peaked around week 30. The slope of the peak in 2021 was markedly steeper than in the previous years. The mean weekly admission rate did not differ significantly between 2018, 2019, and 2021 (p = 0.77). The proportions of intubated patients did not differ significantly over the 4 years (2018­2021, p = 0.68). CONCLUSION: The overall number of RSV admissions and intubation rate in 2021 were similar to those in pre-pandemic years.

Objectives Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions. Methods We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode. Results pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). Glucose levels were correlated with indicators of dehydration and kidney function (blood urea nitrogen (BUN), r=0.44; creatinine, r=0.42; glucose-corrected sodium, r=0.32). Among children with repeat DKA episodes, PCO2 levels tended to be similar at the first vs. second episode (r=0.34), although pH levels were only loosely correlated (r=0.19). Conclusions Elevated glucose levels at DKA presentation largely reflect alterations in glomerular filtration rate. pH and PCO2 are weakly correlated suggesting that respiratory responses to acidosis vary among individuals and may be influenced by pulmonary and central nervous system effects of DKA.

Although acute cardiac tamponade is one of the major problems in clinical practice, a suitable animal model is still lacking. We tried to create acute cardiac tamponade in macaques by echo-guided catheter manipulation. A 13-year-old male macaque was anesthetized, and a long sheath was inserted into the left ventricle via the left carotid artery under the guidance of transthoracic echocardiography. The sheath was then inserted into the orifice of the left coronary artery to perforate the proximal site of the left anterior descending branch. A cardiac tamponade was successfully created. Injection of diluted contrast agent into the pericardial space via a catheter made it possible to clearly distinguish between the hemopericardium and the surrounding tissues on postmortem computed tomography. This procedure did not need an X-ray imaging system during catheterization. Our present model would help us examine the intrathoracic organs in the presence of acute cardiac tamponade.

The B.1.1.7 (Alpha) variant has been detected in Mumbai, India during February 2021. Subsequently, we retrieved 43 sequences from specimens of 51 COVID-19 cases from Mumbai. The sequence analysis revealed that the cases were mainly affected with Alpha variant which suggests its role in community transmission of SARS-CoV-2 in Mumbai, India.

Elemene is a second-line broad-spectrum anti-tumour drug that has been used in China for more than two decades. However, its main anti-tumour ingredient, β-elemene, has disadvantages, including excessive lipophilicity and relatively weak anti-tumour efficacy. To improve the anti-tumour activity of β-elemene, based on its minor molecular weight character, we introduced furoxan nitric oxide (NO) donors into the β-elemene structure and designed six series of new generation β-elemene NO donor hybrids. The synthesised compounds could effectively release NO in vitro, displayed significant anti-proliferative effects on U87MG, NCI-H520, and SW620 cell lines. In the orthotopic glioma model, compound Id significantly and continuously suppressed the growth of gliomas in nude mice, and the brain glioma of the treatment group was markedly inhibited (>90%). In short, the structural fusion design of NO donor and β-elemene is a feasible strategy to improve the in vivo anti-tumour activity of β-elemene.

People previously treated for TB are at a higher risk of rifampicin-resistant or multidrug-resistant TB (RR/MDR-TB). Uganda’s recent RR-TB estimates were not updated, including during the COVID-19 pandemic. Using programmatic data (2012–2021), we report on the distribution and trends in RR-TB among people previously treated for bacteriologically confirmed pulmonary TB (BC-PTB) across six TB clinics in Kampala, Uganda. The RR-TB prevalence between 2012 and 2015 was 0% (95% CI 0–2.3). The prevalence rose significantly in recent years to 7.0% (95% CI 4.4–10.8) between 2016 and 2021 (P < 0.001). RR-TB is increasing among people previously treated for BC-PTB in Kampala; surveillance for RR-TB should be enhanced.

Although detection of drug-susceptible TB by Anti-Persoonsmijnen Ontmijnende Product Ontwikkeling-trained African giant pouched rats has been known for more than a decade, the detection of drug-resistant TB (DR-TB) using rats has never been explored before. We present what we believe to be the first report on rifampicin-resistant TB (RR-TB) detected using Xpert® MTB/RIF Ultra, comparably identified by rats sniffing sputum samples from presumptive TB patients: 88% of RR-TB detected using Ultra were identified by the rats. Further evaluation of the usefulness of rats for large-scale DR-TB contact triage testing is needed, especially in low- and middle-income countries, where resources are limited.

N6-methyladenosine (m6A) is an abundant mRNA modification affecting mRNA stability and protein expression. It is a highly dynamic process, and its outcomes during postnatal heart development are poorly understood. Here we studied m6A machinery in the left ventricular myocardium of Fisher344 male and female rats (postnatal days one to ninety; P1-P90) using Western Blot. A downward pattern of target protein levels (demethylases FTO and ALKBH5, methyltransferase METTL3, reader YTHDF2) was revealed in male and female rat during postnatal development. On P1, the FTO protein level was significantly higher in male compared to females.

An outbreak occurred in Wanhua District of Taipei City. It was traced to a cluster infection originating from a teahouse. To prevent further large-scaled community spread, the Taipei City Government established the first community rapid test screening station. This report describes the station's strategy and performance and key factors that contributed to its operation. The project involves collaboration among various departments of Taipei City Government, including the health, environmental, police, transportation, and fire departments. The station provides rapid screening, polymerase chain reaction (PCR) testing, and immediate isolation and follow-up medical services upon the detection of a positive case. These services are accessible to local residents and are intended to ease hospitals' burdens. In 36 days, a total of 8532 people were tested, and 419 confirmed cases were identified. Over the same period, the weekly number of positive cases in Wanhua District decreased from 356 to 40, and the PCR positive rate decreased from 21.7% to 1.2%. The policy of establishing rapid screening station, contact tracing and mask wearing policy are key strategies for interrupting chains of transmission of COVID-19. This intervention has become a model for preventing the spread of the epidemic and establishing community rapid screening stations in Taiwan.

The aim of this study was to evaluate the impact of diabetes mellitus type 2 (DM2) on the male endocrine system of Zucker Diabetic Fatty (ZDF) rats. Sexually mature ZDF rats were divided to a lean (control) and obese group, and had diabetes confirmed by blood tests. For the in vivo experiment, fasting blood was collected to obtain blood plasma. In case of the in vitro experiments, testicular fragments were cultured for 24 h, and the culture medium was collected. The concentrations of testosterone (T), androstenedione (A4), dehydroepiandrosterone (DHEA-S), estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were quantified in the blood plasma and the medium by the ELISA method, while cholesterol (CHOL) was assessed spectrophotometrically. A significant decline of T (36.31 %), A4 (25.11 %) and FSH (26.99 %) as well as a significant increase of CHOL and E2 (36.17 %) was observed in the blood plasma of obese ZDF rats in comparison to the control. Under in vitro conditions, a significant decrease of FSH (23.35 %) accompanied by an increase of E2 was observed in the obese group compared to the control. In the case of CHOL, LH, T, DHEA and A4 no significant differences were observed. Our results suggest that except for FSH and E2 all steroid biomolecules were synthetized normally by the testicular tissue, however a dramatic endocrine disturbance was observed at the system level. We may conclude that DM2 has negative effects on systemic hormone secretion and these alterations are more pronounced in combination with obesity.

Lysosomes are crucial for degradation and recycling of damaged proteins and cellular components. Therapeutic strategies enhancing lysosomal function are a promising approach for aging and age-related neurodegenerative diseases. Here, we show that an FDA approved drug sodium polystyrene sulfonate (SPS), used to reduce high blood potassium in humans, enhances lysosomal function both in C. elegans and in human neuronal cells. Enhanced lysosomal function following SPS treatment is accompanied by the suppression of proteotoxicity caused by expression of the neurotoxic peptides Aβ and TAU. Additionally, treatment with SPS imparts health benefits as it significantly increases lifespan in C. elegans. Overall our work supports the potential use of SPS as a prospective geroprotective intervention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00647-8.

The brassinosteroid (BR) phytohormone is an important regulator of plant growth. To identify novel transcription factors that regulate BR responses, we screened chimeric repressor gene silencing technology (CRES-T) plants, in which transcription factors were converted into chimeric repressors by the fusion of SRDX plant-specific repression domain, with brassinazole (Brz), an inhibitor of BR biosynthesis. We identified that a line that expressed the chimeric repressor for zinc finger homeobox transcription factor, BRASSINOSTEORID-RELATED-HOMEOBOX-2 (BHB2-sx), exhibited Brz-hypersensitive phenotype with shorter hypocotyl under dark, dwarf and round and dark green leaves similar to BR-deficient phenotype. Similar to BHB2-sx plants, bhb2 knockout mutant also exhibited Brz hypersensitive phenotype. In contrast, ectopic expression of BHB2 (BHB2-ox) showed hypocotyl elongation phenotype (BR excessive), showing decrease to Brz sensitivity. The expression of the DWF4 and CPD BR biosynthesis genes was repressed in BHB2-sx plants, whereas it was enhanced in BHB2-ox plants. The BR deficient-like phenotype of BHB2-sx plants was partially restored by treatment with brassinolide (BL), indicating that the BR deficient phenotype of BHB2-sx plant may be due to suppression of BR biosynthesis. Our results indicate that BHB2 is a positive regulator of BR response may be due to the promotion of BR biosynthesis genes.

Although rapid, the evaluation of bone marrow (BM) cellularity is semi-quantitative and largely dependent upon visual estimates. We aimed to construct an automatic quantification method using image analysis software. We used hematoxylin and eosin (HE)-stained specimens of BM biopsies and clots from patients who underwent BM examination at Tottori University Hospital from 2020 to 2022. We compared image analysis (Methods A, B, and C) with visual estimates in pathology reports of 91 HE specimens in 54 cases (29 males, 25 females), including 38 biopsy and 53 clot specimens. Cellularity was visually scored as hypocellular (n = 17), normocellular (n = 44), or hypercellular (n = 30). Compared with the visual estimates, intraclass correlation coefficients for Methods A, B, and C were 0.80, 0.85, and 0.88, respectively. The most appropriate values were obtained with Method C which detected both non-fatty and cell nuclear areas.

Aim: Molecular alterations in drug targets may result in differential drug activity. Therefore, the authors aimed to characterize how molecular alterations in drug targets were assessed during drug development. Materials & methods: The authors analyzed nonclinical and clinical study reports submitted to the US FDA for novel drugs approved in 2020 to determine if in vitro studies, animal models or clinical studies assessed molecular alterations in the drug target. Results & conclusion: Assessment of the impact of molecular alterations in drug targets on drug activity varies considerably depending on the type of assessment and therapeutic area. Premarket assessment of drug target molecular alterations is common in the oncology setting, less frequent in the genetic disease setting and rare for other diseases.

Objectives: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC). Methods: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose. Results: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%. Conclusion: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area. Advances in knowledge: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.

BACKGROUND: People who use drugs (PWUD) in the San Diego, USA and Tijuana, Mexico metroplex face high overdose risk related to historic methamphetamine use and relatively recent fentanyl introduction into local drug supplies. The personal overdose experiences of PWUD in this region are understudied, however, and may have been influenced by the COVID pandemic. METHODS: From September-November 2021, we conducted 28 qualitative interviews among PWUD ≥18 years old sampled from an ongoing cohort study in the San Diego-Tijuana metroplex. Interviews explored overdose experiences and changes in the drug supply. Thematic analysis of coded interview transcripts explored overdose experiences, perspectives on drug supply changes, interactions with harm reduction services, and naloxone access. RESULTS: Among 28 participants, 13 had experienced an overdose. Participants discussed rising levels of fentanyl in local drug supplies and increasing overdose incidents in their social networks. Participants discussed a general shift from injecting heroin to smoking fentanyl in their networks. Participants’ most common concerns included having consistent access to a safe and potent drug supply and naloxone. CONCLUSION: Participants prioritized adapting to drug supply changes and preventing overdose compared to other health concerns, such as HIV and COVID-19. Efforts to address overdose in this region could benefit from drug checking services and expanded, equitable delivery of naloxone.

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Aim: To determine the association of coenzyme Q10 (CoQ10) use with the resolution of statin-associated muscle symptoms (SAMS). Patients & methods: Retrospective analysis of a large, multicenter survey study of SAMS (total n = 511; n = 64 CoQ10 users). Univariate and multivariate logistic regression models assessed the association between CoQ10 use and the resolution of SAMS. Results: The frequency of SAMS resolution was similar between CoQ10 users and non-users (25% vs 31%, respectively; unadjusted odds ratio [OR]: 0.75 [95% CI: 0.41–1.38]; p = 0.357). Similarly, CoQ10 use was not significantly associated with the resolution of SAMS in multivariable models adjusted for SAMS risk factors (OR: 0.84 [95% CI: 0.45–1.55]; p = 0.568) or adjusted for significant differences among CoQ10 users and non-users (OR: 0.82 [95% CI: 0.45–1.51]; p = 0.522). Conclusion: CoQ10 was not significantly associated with the resolution of SAMS.

This study aimed to investigate the mechanism by which camel whey protein (CWP) inhibits the release of high-mobility group box 1 (HMGB1) in heat stress (HS)-stimulated rat liver. Administration of CWP by gavage prior to HS inhibited the cytoplasmic translocation of HMGB1 and consequently reduced the inflammatory response in the rat liver, and downregulated the levels of the NLR pyrin domain containing 3 (NLRP3) inflammasome, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. The use of N-acetyl-L-cysteine (NAC), an inhibitor of reactive oxygen species (ROS) production, indicated that this downregulation effect may be attributed to the antioxidant activity of CWP. We observed that CWP enhanced nuclear factor erythroid 2-related factor (Nrf)2 and heme-oxygenase (HO)-1 expression, which inhibited ROS production, nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity, and malondialdehyde (MDA) levels, and increased superoxide dismutase 1 (SOD1) activity and reduced glutathione (GSH) content in the HS-treated liver, ultimately increasing the total antioxidant capacity (TAC) in the liver. Administration of Nrf2 or HO-1 inhibitors before HS abolished the protective effects of CWP against oxidative damage in the liver of HS-treated rats, accompanied by increased levels of HMGB1 in the cytoplasm and IL-1β and TNF-α in the serum. In conclusion, our study demonstrated that CWP enhanced the TAC of the rat liver after HS by activating Nrf2/HO-1 signaling, which in turn reduced HMGB1 release from hepatocytes and the subsequent inflammatory response and damage. Furthermore, the combination of CWP and NAC abolished the adverse effects of HS in the rat liver. Therefore, dietary CWP could be an effective adjuvant treatment for HS-induced liver damage.

Case-based cadaver dissection offers students unique opportunities to blend traditional anatomic knowledge acquisition with clinical reasoning. Twelve physical therapy students completed surveys centered on case-based dissections. Case-based cadaver dissections were defined in this study as multiple clinical vignettes that required students to use the accessible cadavers to solve clinically based problems. The results of the study provide preliminary evidence that students perceive case-based cadaver dissections as beneficial to their anatomy education and beneficial to the development of their clinical reasoning skills. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-022-01540-x.

This study evaluated the effectiveness of spraying juices, during shortwave ultraviolet irradiation (UVC) treatments as an alternative to promote more contact area, by means of ultrasonic atomization (UA) and pneumatic atomization (PA). Four juices with dissimilar physical characteristics were processed to assess the effect of suspended solids and turbidity. Antioxidant activity, anthocyanins, ascorbic acid, and inactivation of Saccharomyces cerevisiae inoculated in the juices were evaluated. Five decimal reduction cycles were reached after two passes of orange or grapefruit juice through the UVC + UA arrangement. On the other hand, five decimal reduction cycles were achieved after three passes in the UVC + PA arrangement. Losses of 11% and 14% of ascorbic acid were observed in orange and grapefruit juice, respectively, while anthocyanin content presented losses of 50% and antioxidant activity decreased by 40% for pomegranate and blueberry juice, correspondingly.

Aims: Better documentation of vulvar pain is needed. We examined pain locations marked on general body and genital specific outlines among women with vulvodynia. Methods: 62 women (mean age 32.1 ± 9.5 years) with vulvodynia marked their pain on a digital genital specific outline (22 segments) and 59 of those women also marked their pain on a digital general body outline (48 segments). We used ImageJ software to determine body surface area (BSA) for each outline. Results: On the general body outline, 24/48 segments were marked; 22/22 segments were marked on the genital specific outline. There was a moderate correlation ( r = 0.43; p = 0.001) between the BSA marked on the general body outline and the BSA marked on the genital area outline. Conclusions: Findings support concurrent validity of the BSA as a measure of pain location using either outline.

Glucagon-like-peptide 2 (GLP-2) is an endogenous enteroendocrine physiological trophic peptide. Glepaglutide is a novel long-acting GLP-2 analog under development for the treatment of patients with Short Bowel Syndrome (SBS). The objective of this work was to compare the small intestinal trophic effects in both genders following short (1 week) versus long-term (26-39 weeks) GLP-2 treatment in Wistar rats and Beagle dogs. Following both short- and long-term treatment with glepaglutide, a significant dose-dependent intestinotrophic effect was seen in both genders and species. At all doses increased length and weight of the small intestine as well as macroscopic thickening and villous hypertrophy were noted in all segments of the small intestine, without any differences between genders. The findings were still present following a 6-week recovery period, indicating long-acting intestinotrophic effects of glepaglutide. These studies demonstrate that a long-acting GLP-2 analogue (glepaglutide) has a fast onset and long duration of intestinotrophic action with similar profile in both genders and species (rat and dog).

Exercise tolerance in patients with idiopathic pulmonary fibrosis IPF is mainly limited by mechanical constrain of ventilation and high physiologic dead space. Oxygen enriched gas inhalation seems to increase ventilatory efficiency by reduction of dead space to tidal volume ratio (VD/VT) which probably mirrors improved pulmonary capillary flow and leads to longer physical tolerance at lower level of minute ventilation. The effect is noticeable at FIO2 that can be delivered in rehabilitation purposes or daily living activities.